This project will investigate the effects of HIV gp120 on the production of new cells by the thymus. It is known that the receptor for HIV gp120, CD4, is involved in thymocyte maturation, particularly in the maturation of those cells which are the precursors for CD4+ mature peripheral T cells. The exact function of CD4 in thymocyte development is not, however, understood. In this project the effects of HIVgp120, or anti-CD4 on the development of thymocytes in human CD4 transgenic mice, in cultured thymuses from these mice, or in cultured human thymuses will be studied. Signal transduction in different subpopulations of thymocytes initiated by the interaction of gp120 or anti-CD4 with CD4 will also be measured. The results of these experiments will indicate whether or not HIV infection, and production of gp120, will inhibit production of mature T cells by the thymus. The results may also shed some light on the role played by CD4 in thymocyte maturation.